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Front Physiol. 2013 Jul 16;4:175. doi: 10.3389/fphys.2013.00175. eCollection 2013.

The sigma-1 receptor: a regulator of cancer cell electrical plasticity?

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Université de Nice, UMR 7277 Nice, France ; Institut de Biologie de Valrose, CNRS UMR 7277, INSERM U1091, Université de Nice Nice, France.


Originally mistaken as an opioid receptor, the sigma-1 receptor (Sig1R) is a ubiquitous membrane protein that has been involved in many cellular processes. While the precise function of Sig1R has long remained mysterious, recent studies have shed light on its role and the molecular mechanisms triggered. Sig1R is in fact a stress-activated chaperone mainly associated with the ER-mitochondria interface that can regulate cell survival through the control of calcium homeostasis. Sig1R functionally regulates ion channels belonging to various molecular families and it has thus been involved in neuronal plasticity and central nervous system diseases. Interestingly, Sig1R is frequently expressed in tumors but its function in cancer has not been yet clarified. In this review, we discuss the current understanding of Sig1R. We suggest herein that Sig1R shapes cancer cell electrical signature upon environmental conditions. Thus, Sig1R may be used as a novel therapeutic target to specifically abrogate pro-invasive functions of ion channels in cancer tissue.


cancer; chaperones; ion channels modulation; physiological; sigma-1 receptor; stress

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